MiRNA Deregulation in Cardiac Aging and Associated Disorders.

The prevalence of age-related diseases is increasing dramatically, among which cardiac disease represents the leading cause of death. Aging of the heart is characterized by various molecular and cellular hallmarks impairing both cardiomyocytes and noncardiomyocytes, and resulting in functional deteriorations of the cardiac system. The aging process includes desensitization of β-adrenergic receptor (βAR)-signaling and decreased calcium handling, altered growth signaling and cardiac hypertrophy, mitochondrial dysfunction and impaired autophagy, increased programmed cell death, low-grade inflammation of noncanonical inflammatory cells, and increased ECM deposition. MiRNAs play a fundamental role in regulating the processes underlying these detrimental changes in the cardiac system, indicating that MiRNAs are crucially involved in aging. Among others, MiR-34, MiR-146a, and members of the MiR-17-92 cluster, are deregulated during senescence and drive cardiac aging processes. It is therefore suggested that MiRNAs form possible therapeutic targets to stabilize the aged failing myocardium.